Method of preparing aminophenolethers



Patented July 30, 1929.

UNITED STATES PATENOFFICE.

ERNST F. GRETHER, OF MIDLAND, MICHIGAN, ASSIGNOR TO {THE DOW CHEMICAL COMPANY, OF MIDLAND, MICHIGAN, .A. CORPORATION OF MICHIGAN.

METHOD OF PREPARING AMIJV'OPEENOLETHERS.

No Drawing.

This invention relates to the preparation of compounds on the order of aminophenolothers. It has been proposed (German Patent 48,543) to make p-phenetidine by starting with 1 mol. of p-pheneti'dine, diazotizing and coupling with 1 mol. of phenol, ethylating the resulting compound, and reducing by tin and hydrochloric acid the azophenetol to 2 mol. of phenetidine, of which one was to be carried back into the process. Such procedure has the initial obstacle of starting with expensive phenetidine, and as pointed out by J acobson and Fischer, Ber. 25, 992,

reduction of an azophenetol by tin and hydrochloric acid produces only a small amount of amines, there being instead a predominant decomposition. A procedure of general applicability for making aminophenol- 'ethers is accordingly highly. desirable.

To the accomplishment of the foregoing and related ends, the invention, then, consists in the features hereinafter fully de-v scribed, and particularly pointed out in the claims, the following description setting forth but a few of the various ways in which the principle-of the invention may be used.

In accordance with my invention, an arylamine is diazotized, coupled with a phenol, alkylated, and this resulting compound is treated to convert it into an aminophenolether and the. arylamine started with. The particular henol and alkyl halide used determine t e particular .aminophenolether produced. The arylamine employed initially is recovered and may be used over and over again with very little loss.

The course of the reactions involved may be illustrated schematically by the following, inwhich R and R represent aryl radicals which may if desired be the same:

diazotize RNH, RN:NCI

couple alkylate Alk- RN! NR'OH--'- RNiNR'o reduce v As an illustration .of the invention, the following is given as-an example of the procedure involved, using aniline in this particular instance:

' Aniline is treated with sodium nitrite and hydrochloric acid, and coupled with phenol in the proportion of 1 mol. to 1 mol., the resulting compound is treated with ethyltinctly claim as my invention:

Application filed June 2, 1526. Serial ms. 113,344.

bromide, and this product in turn is stirred and heated to a temperature between 50 to C. for about twelve hours with about one-twentieth part (by weight) of iron acetate, three parts of iron, three parts of water, and one part of benzene. Sodium carbonate is then added to precipitate the iron, and the para ethoxyphenylamine (paraphenetidine) and aniline are extracted with benzene and distilled and separated. The benzene used serves to hasten the reaction somewhat, by dissolving the azo compounds and can be replaced by other solvents as toluene, alcohol, etc.

Instead of aniline, o-toluidine or other arylamines can be employed in the .process, and likewise other phenols as cresols, na hthols, etc., may be used. Similarly ot er alkyl halides as methyl bromide, or alkylatmg agents, as ethyl sulphate, may be employed in lieu of ethyl bromide. 'In some cases I also contemplate the use of other iron salts, more especially chloride, instead .of Iron acetate.

The temperature of the final heatin is in a sense a reciprocal of the time; that 1s, the higher the temperature, the shorter the time r uired. For instance, with a temperature of 0-80 (3., the time required will be only about 5 to 7 hours. However, temperatures as high as 100 C. are prone to cause decomposition, and it is accordingly preferable to operate at lower temperatures.

Other modes-of applyin the principle of my invention ma be emp oyed instead of that here explaine change being made in the features described, provided the steps stated by any of the following claims or the eguivalent of such stated steps be eme I therefore particularly point out and dis- 1,*In a method of preparing amino phe nolethers, the steps which consist in diamtizing an arylamine, coupling with a. phenol, ulkilating, and then reducing by heating wit iron and an iron salt in the, presence of water. v 2. In a method of preparing aminophenolethers, the steps which consist in-diazotizing an arylamine, coupling with a phenol, alki ating, and then reducing by heating 'wit iron and iron acetate in thepresence of water.

' 3. In a method of preparing aminophenolethers,-the steps whichconsist in diamtizing aniline, coupling with a phenol, alkylating, and then reducing b heating with iron and an iron salt in t e presence of water.

4. In a method of preparing aminophenolethers, the steps which consist in diamtizing aniline, coupling with a phenol, alkylating, and then reducing by heating with iron and iron acetate in the presence of water.

5. In a methodof preparing aminophenolethers, the steps which consis in diamtizing aniline, coupling with a phenol, alkylating, and then reducing with about onetwentieth part of iron acetate and three parts of iron and one part of water, at a temperature of to C., while stirring.

6. In a method of preparing para-phenetidine, the steps which consist in diazotizing aniline, coupling withphenol, alkylating, and then reducing with about one-twentieth part of iron acetate and three parts of iron and one part of water, at a temperature of 50 to 60 0., while stirring.

7. In a method of preparing aminophenolethers, the steps which consist in diamtizing an arylamine, coupling with a phenol, alkylating, and then reducing by heating with iron and an iron salt,'in the presence of water and an organic solvent unreactive with the mixture components.

8. In a' method of preparing aminophenolethers, the steps which consist in diamtizing aniline, coupling with a phenol, alkylating, and then reducing by heating with iron and an iron salt in the presence of water and an organic solvent unreactive with the mixture components.

9. The method of preparing para-phenetidine, which comprises diazotizlng aniline, coupling with phenol, alkylating, and then reducing with iron and an lIOIl salt in the presence of water and an organic solvent unreactive with the mixture components, at a temperature below C.

10. A method of preparing para-phonetidine, which comprises diazotizing aniline, coupling with phenol, alkylating, and then reducing with iron and an iron salt in the presence of benzene at a temperature below 100 C.

Signed by me this 27th day of May, 1926.

ERNST F; GRETHER. 

